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Immunology2023; doi: 10.1111/imm.13745

Single-cell profiling of bronchoalveolar cells reveals a Th17 signature in neutrophilic severe equine asthma.

Abstract: Severe equine asthma (SEA) is a complex respiratory condition characterized by chronic airway inflammation. It shares many clinical and pathological features with human neutrophilic asthma, making it a valuable model for studying this condition. However, the immune mechanisms driving SEA have remained elusive. Although SEA has been primarily associated with a Th2 response, there have also been reports of Th1, Th17, or mixed-mediated responses. To uncover the elusive immune mechanisms driving SEA, we performed single-cell mRNA sequencing (scRNA-seq) on cryopreserved bronchoalveolar cells from 11 Warmblood horses, 5 controls and 6 with SEA. We identified six major cell types, including B cells, T cells, monocytes-macrophages, dendritic cells, neutrophils, and mast cells. All cell types exhibited significant heterogeneity, with previously identified and novel cell subtypes. Notably, we observed monocyte-lymphocyte complexes and detected a robust Th17 signature in SEA, with CXCL13 upregulation in intermediate monocytes. Asthmatic horses exhibited expansion of the B-cell population, Th17 polarization of the T-cell populations, and dysregulation of genes associated with T-cell function. Neutrophils demonstrated enhanced migratory capacity and heightened aptitude for neutrophil extracellular trap formation. These findings provide compelling evidence for a predominant Th17 immune response in neutrophilic SEA, driven by dysregulation of monocyte and T-cell genes. The dysregulated genes identified through scRNA-seq have potential as biomarkers and therapeutic targets for SEA and provide insights into human neutrophilic asthma.
© 2023 The Authors. Immunology published by John Wiley & Sons Ltd.
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Publication Date: 2023-12-28 PubMed ID: 38153159DOI: 10.1111/imm.13745Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article focuses on a detailed analysis of bronchoalveolar cells in horses suffering from severe equine asthma (SEA), revealing a predominant Th17 immune response and potentially providing new biomarkers and therapeutic targets for treating the condition.

Research Objective and Methodology

The researchers aimed to uncover the elusive immune mechanisms driving SEA, a complex respiratory condition characterized by chronic airway inflammation. The study uses SEA as a model for studying human neutrophilic asthma given the similar clinical and pathological features. For this, the researchers used single-cell mRNA sequencing (scRNA-seq) on bronchoalveolar cells from 11 Warmblood horses; five were controls and six were afflicted with SEA.

Findings of the Study

  • Through the procedure, the researchers identified six primary cell types: B cells, T cells, monocytes-macrophages, dendritic cells, neutrophils, and mast cells. Significant heterogeneity was found within all cell types, including previously identified and novel cell subtypes.
  • Notably, the researchers observed complexes formed by monocytes and lymphocytes and detected a strong Th17 signature in SEA. An upregulation in CXCL13, a gene responsible for controlling chemotaxis, was found in intermediate monocytes.
  • In horses with asthma, the researchers found an expansion of the B-cell population and Th17 polarization of the T-cell populations. They also found a dysregulation of genes associated with T-cell function.
  • The researchers also found that the neutrophils demonstrated enhanced migratory capacity and a heightened ability to form neutrophil extracellular traps, a component of the immune response.

Conclusion and Implications

The results reveal a predominant Th17 immune response in cases of neutrophilic SEA. This response is driven by the dysregulation of particular genes in monocytes and T-cells. The dysregulated genes identified through scRNA-seq potentially serve as biomarkers for SEA and possible targets for therapeutic intervention. Consequently, the findings of this study also shed light on the understanding and treatment of human neutrophilic asthma.

Cite This Article

APA
Sage SE, Leeb T, Jagannathan V, Gerber V. (2023). Single-cell profiling of bronchoalveolar cells reveals a Th17 signature in neutrophilic severe equine asthma. Immunology. https://doi.org/10.1111/imm.13745

Publication

Immunology
ISSN: 1365-2567
NlmUniqueID: 0374672
Country: England
Language: English

Researcher Affiliations

Sage, Sophie E
  • Department of Clinical Veterinary Medicine, Vetsuisse Faculty, Swiss Institute of Equine Medicine, University of Bern, Bern, Switzerland.
Leeb, Tosso
  • Institute of Genetics, Vetsuisse Faculty, Institute of Genetics, University of Bern, Bern, Switzerland.
Jagannathan, Vidhya
  • Institute of Genetics, Vetsuisse Faculty, Institute of Genetics, University of Bern, Bern, Switzerland.
Gerber, Vinzenz
  • Department of Clinical Veterinary Medicine, Vetsuisse Faculty, Swiss Institute of Equine Medicine, University of Bern, Bern, Switzerland.

Grant Funding

  • 31003A-162548/1 / Swiss National Science Foundation

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